Pharmacodynamic Response to Warfarin After Conversion of Atrial Fibrillation or Flutter to Sinus Rhythm

Melissa C. Staats; Michael E. Ernst


Am J Health Syst Pharm. 2012;69(13):1158-1161. 

In This Article

Abstract and Introduction


Purpose The results of an evaluation of the impact of restoring sinus rhythm on warfarin sensitivity are reported.
Methods A retrospective review of the records of all patients (n = 46) with atrial fibrillation or flutter who underwent cardioversion or ablation procedures to restore sinus rhythm at a large medical center during a 27-month period was conducted. Patient data covering the 3-month periods before and after the procedures were reviewed to identify the warfarin doses required to maintain International Normalized Ratio (INR) values in the recommended range of 2.0–3.0. Within-individual preprocedure and postprocedure mean weekly warfarin doses for two periods (zero to four weeks and an expanded period of four weeks–3 months) were compared using paired t tests.
Results The average weekly warfarin dose during the four-week preprocedure period was not significantly different from the doses during the four-week and expanded postprocedure periods. The average weekly doses during the four-week and expanded postprocedure periods were significantly less than those used in the expanded preprocedure period (p = 0.004 and p = 0.046, respectively).
Conclusion Warfarin dosages required to maintain a goal INR of 2.0–3.0 were relatively stable in the four weeks before and after procedures to convert atrial fibrillation or flutter to sinus rhythm. Changes in the weekly warfarin dose requirement of ≥10% after the procedures were implemented in a small proportion of patients. The mean weekly warfarin dose was significantly lower in the three months after than in the three months before the procedure.


A trial fibrillation and atrial flutter are commonly occurring cardiac arrhythmias.[1,2] As they have the potential to cause hemodynamic instability and thromboembolic events, these arrhythmias are associated with significant morbidity, mortality, and health care costs. Practice guidelines currently recommend anticoagulation with warfarin, with a goal International Normalized Ratio (INR) of 2.0–3.0, for three to four weeks before and after conversion to sinus rhythm in patients experiencing atrial fibrillation for periods of >48 hours or of an unknown duration.[3] Patients preparing to undergo elective cardioversion are thus intensively and regularly monitored to ensure that INR values remain within the goal range. The extent to which the restoration of sinus rhythm affects warfarin sensitivity is unknown. Since cardiac output is reduced in atrial fibrillation, it is possible there is a downstream effect on hepatic perfusion that may subsequently influence the pharmacodynamic response to hepatically metabolized drugs such as warfarin.

Clinical pharmacists are frequently responsible for managing warfarin therapy in patients with atrial fibrillation or flutter pending procedures to restore sinus rhythm. The purpose of the study described here was to evaluate the impact of restoring sinus rhythm on warfarin maintenance requirements. Specifically, we sought to determine (1) whether the within-patient mean warfarin dosage required to maintain INR values within the goal range of 2.0–3.0 was significantly different before and after the restoration of sinus rhythm and (2) if a significant difference was noted, the magnitude and direction of the dosage change. Such information could help improve the safety of warfarin management in patients with atrial fibrillation or flutter.


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